A novel homozygous variation in the PANK2 gene in two Persian siblings with atypical pantothenate kinase associated neurodegeneration

Habibi, Amir Hasan; Razmeh, Saeed; Aryani, Omid; Rohani, Mohammad; Taghavian, Laleh; Alizadeh, Elham; Kokhedan, Karim Moradian; Zaribafian, Maryam

doi:10.4081/ni.2019.7959

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…Reduction of NAA indicated loss of neuronal integrity and function, and the NAA/tCr ratio trended toward improvement but was not significant following BBP-671 treatment. Reduction of NAA in the globus pallidus is consistently reported in patients with PKAN [15][16][17][18].…”

Section: Resultsmentioning

confidence: 99%

“…1 H MRS can identify biomarkers and be applied to evaluate clinical neurodegeneration and therapeutic strategies [13,14]. In the limited clinical studies demonstrating the application of 1 H MRS in studying PKAN, a reduced N-acetyl aspartate (NAA) level was commonly observed [15][16][17][18]. This is the first report using 1 H MRS for monitoring PKAN therapeutics in a mouse model of the disease.…”

Section: Open Accessmentioning

confidence: 99%

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Proton magnetic resonance spectroscopy detects cerebral metabolic derangement in a mouse model of brain coenzyme a deficiency

Li¹,

Steinberg²,

Coleman³

et al. 2022

J Transl Med

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Background Pantothenate kinase (PANK) is the first and rate-controlling enzymatic step in the only pathway for cellular coenzyme A (CoA) biosynthesis. PANK-associated neurodegeneration (PKAN), formerly known as Hallervorden–Spatz disease, is a rare, life-threatening neurologic disorder that affects the CNS and arises from mutations in the human PANK2 gene. Pantazines, a class of small molecules containing the pantazine moiety, yield promising therapeutic effects in an animal model of brain CoA deficiency. A reliable technique to identify the neurometabolic effects of PANK dysfunction and to monitor therapeutic responses is needed. Methods We applied 1H magnetic resonance spectroscopy as a noninvasive technique to evaluate the therapeutic effects of the newly developed Pantazine BBP-671. Results 1H MRS reliably quantified changes in cerebral metabolites, including glutamate/glutamine, lactate, and N-acetyl aspartate in a neuronal Pank1 and Pank2 double-knockout (SynCre+Pank1,2 dKO) mouse model of brain CoA deficiency. The neuronal SynCre+Pank1,2 dKO mice had distinct decreases in Glx/tCr, NAA/tCr, and lactate/tCr ratios compared to the wildtype matched control mice that increased in response to BBP-671 treatment. Conclusions BBP-671 treatment completely restored glutamate/glutamine levels in the brains of the mouse model, suggesting that these metabolites are promising clinically translatable biomarkers for future therapeutic trials.

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Section: Resultsmentioning

confidence: 99%

Section: Open Accessmentioning

confidence: 99%

Proton magnetic resonance spectroscopy detects cerebral metabolic derangement in a mouse model of brain coenzyme a deficiency

Li¹,

Steinberg²,

Coleman³

et al. 2022

J Transl Med

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“…NBIA caused by PANK2 mutations has been reported previously in Asian ethnic groups, for example, Chinese, Korean, Indian, Iranian, Taiwan, and Thailand. [8,[13][14][15][16][17][18][19][20][21][22][23][24] In this article, we report the first PKAN patient in Vietnam due to the PANK2 mutations.…”

Section: Pantothenatementioning

confidence: 99%

The first Vietnamese patient who presented late onset of pantothenate kinase-associated neurodegeneration diagnosed by whole exome sequencing: A case report

Tran,

Vu,

Tran

et al. 2023

Medicine

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Rationale: Pantothenate kinase-associated neurodegeneration (PKAN), also called Hallervorden-Spatz syndrome, is a rare autosomal recessive disease associated with brain iron accumulation and characterized by progressive dystonia, dementia, and dysarthria symptoms. PKAN, caused by a defective pantothenate kinase 2 (PANK2) gene, is the most common neurodegeneration with a brain iron accumulation (NBIA) group. The “eye of the tiger” sign in the magnetic resonance imaging demonstrated a bilateral hyperintense signal in the basal ganglia region on T2-weighted images, which is a characteristic feature of the diagnosis. PKAN is classified into 2 main types. The early-onset type (classic type) with rapid progression is characterized by symptoms of gait impairment and dystonia leading to loss of ambulation in early childhood. In the later-onset type (atypical type), slow progression usually takes place in the second decade of life with symptoms of neurodegeneration, dystonia, dysarthria, rigidity, choreoathetosis, and motor impairment. Until now, PKAN patients have only been reported in a few countries in Asia such as China, Korea, India, Iran, Taiwan, and Thailand. Patient concerns: Here we report the first case of PKAN in Vietnam. The patient had a late onset but the disease progresses rapidly with symptoms of dyskinesia, dysphagia, and difficulty speaking. Diagnoses: Pantothenate kinase-associated neurodegeneration. Interventions: Whole exome sequencing was performed to identify heterozygous mutations in the PANK2 gene (NM_153638.4) (c.856C>T, p.Arg286Cys and c.1351C>T, p.Arg451Ter) that has been confirmed as the cause of the disease. Outcomes: In this study, the first Vietnamese patient with late-onset PKAN was diagnosed by the whole exome sequencing method. Lessons: The patient’s case marks an important milestone for the first case in Vietnam. The results of the study will provide a scientific basis for clinicians in the diagnosis and genetic counseling of patients.

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“…Respectively, there were 23, 5, 3, 1, 3, 3, and one family with PKAN, MPAN, PLAN, JABELS, BPAN, Kufor-Rakeb and WSSs in Iran (Figure 4). 74,[91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109] Like the other countries, the most common form of NBIA was PKAN accounting for more than half of the cases (59%) (Figure 4). A high percentage of the PKAN may be due to the easy diagnostics procedures; the specific pattern on MRI, which is the "eye of tiger" sign.…”

Section: Nbia In Iranmentioning

confidence: 99%

Neurodegeneration with Brain Iron Accumulation and a Brief Report of the Disease in Iran

Hajati

Emamikhah

Fard

et al. 2021

Can. J. Neurol. Sci.

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Neurodegeneration with brain iron accumulation (NBIA) is a term used for a group of hereditary neurological disorders with abnormal accumulation of iron in basal ganglia. It is clinically and genetically heterogeneous with symptoms such as dystonia, dysarthria, Parkinsonism, intellectual disability, and spasticity. The age at onset and rate of progression are variable among individuals. Current therapies are exclusively symptomatic and unable to hinder the disease progression. Approximately 16 genes have been identified and affiliated to such condition with different functions such as iron metabolism (only two genes: Ferritin Light Chain (FTL) Ceruloplasmin (CP)), lipid metabolism, lysosomal functions, and autophagy process, but some functions have remained unknown so far. Subgroups of NBIA are categorized based on the mutant genes. Although in the last 10 years, the development of whole-exome sequencing (WES) technology has promoted the identification of disease-causing genes, there seem to be some unknown genes and our knowledge about the molecular aspects and pathogenesis of NBIA is not complete yet. There is currently no comprehensive study about the NBIA in Iran; however, one of the latest discovered NBIA genes, GTP-binding protein 2 (GTPBP2), has been identified in an Iranian family, and there are some patients who have genetically remained unknown.

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A novel homozygous variation in the PANK2 gene in two Persian siblings with atypical pantothenate kinase associated neurodegeneration

Cited by 4 publications

References 21 publications

Proton magnetic resonance spectroscopy detects cerebral metabolic derangement in a mouse model of brain coenzyme a deficiency

Proton magnetic resonance spectroscopy detects cerebral metabolic derangement in a mouse model of brain coenzyme a deficiency

The first Vietnamese patient who presented late onset of pantothenate kinase-associated neurodegeneration diagnosed by whole exome sequencing: A case report

Neurodegeneration with Brain Iron Accumulation and a Brief Report of the Disease in Iran

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